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Abstract/Summary
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<jats:p>Monocytes are antigen-presenting cells (APCs) that play diverse roles in promoting or regulating inflammatory responses, but their role in T cell stimulation is not well defined. In inflammatory conditions, monocytes frequently show increased expression of CD169/Siglec-1, a type-I interferon (IFN-I)-regulated protein. However, little is known about the phenotype and function of these CD169<jats:sup>+</jats:sup> monocytes. Here, we have investigated the phenotype of human CD169<jats:sup>+</jats:sup> monocytes in different diseases, their capacity to activate CD8<jats:sup>+</jats:sup> T cells, and the potential for a targeted-vaccination approach. Using spectral flow cytometry, we detected CD169 expression by CD14<jats:sup>+</jats:sup> CD16<jats:sup>-</jats:sup> classical and CD14<jats:sup>+</jats:sup> CD16<jats:sup>+</jats:sup> intermediate monocytes and unbiased analysis showed that they were distinct from dendritic cells, including the recently described CD14-expressing DC3. CD169<jats:sup>+</jats:sup> monocytes expressed higher levels of co-stimulatory and HLA molecules, suggesting an increased activation state. IFNα treatment highly upregulated CD169 expression on CD14<jats:sup>+</jats:sup> monocytes and boosted their capacity to cross-present antigen to CD8<jats:sup>+</jats:sup> T cells. Furthermore, we observed CD169<jats:sup>+</jats:sup> monocytes in virally-infected patients, including in the blood and bronchoalveolar lavage fluid of COVID-19 patients, as well as in the blood of patients with different types of cancers. Finally, we evaluated two CD169-targeting nanovaccine platforms, antibody-based and liposome-based, and we showed that CD169<jats:sup>+</jats:sup> monocytes efficiently presented tumor-associated peptides gp100 and WT1 to antigen-specific CD8<jats:sup>+</jats:sup> T cells. In conclusion, our data indicate that CD169<jats:sup>+</jats:sup> monocytes are activated monocytes with enhanced CD8<jats:sup>+</jats:sup> T cell stimulatory capacity and that they emerge as an interesting target in nanovaccine strategies, because of their presence in health and different diseases.</jats:p>
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Hinweis
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DeepGreen-ID: f5b5ce838cbd487d8f57327e5af66e32 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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